Treatment of arthritis with combinations of antihistaminic compounds and diuretics

ABSTRACT

Therapeutic treatment of arthritis. Involves internally administering specified antihistaminic compounds in conjunction with specified diuretic compounds.

United States Patent [191 [u 3,726,76 Glasser I {45] Apr. 10, 1973 TREATMENT OF ARTHRITIS WITH [56] References Cited COMBINATIONS OF ANTIIHSTAMINIC COMPOUNDS AND DIURETICS US. Cl. ..424/246, 424/263, 424/330 Int. Cl. ..A6lk 27/00 Field of Search ..424/240, 263, 330

OTHER PUBLICATIONS Grollman, Pharmacology and Therapeutics, 6th Ed, (1965), Pp- 444-445.

Primary Examiner-Stanley J. Friedman Attorney-l-Iubbell, Cohen & Stiefel Therapeutic treatment of arthritis. Involves internally administering specified antihistaminic compounds in conjunction with specified diuretic compounds.

ABSTRACT 8 Claims, No Drawings TREATMENT OF ARTHRITIS WITH COMBINATIONS OF ANTIHISTAMINIC COMPOUNDS AND DIURETICS BACKGROUND OF THE INVENTION 1. Field of the'lnvention This invention relates to a method of treating arthritis so as to substantially alleviate pain and suffering therefrom. 2. Description of the Prior Art 7 Heretofore a great number of different methods have been attempted in an effort to provide effective 7 therapeutic treatment for arthritis. By way of example,

the prior art has employed for such treatment indocin, butozolidine, salicylates, gold therapy, steroids, ACTH, quinine derivatives, etc., all without achieving a very satisfactory therapeutic effect.

SUMMARY OF THE INVENTION DESCRIPTION OF THE PREFERRED EMBODIMENTS Satisfactory classification of the arthritides and related conditions is still considered unsatisfactory. The reasonv for this is that the etiological and basic pathological factors are not clearly understood. Be that as it may, wherever there is joint stiffness of the arthritic or related type accompanied by pain, swelling, or deformity, the method of my invention, involving administering the antihistaminic compound and diuretic compound in physiological doses, either intramuscularly or orally, has proven effective. Stiffness of the affected joint and its surrounding structures subsides, pain diminishes, and function improves. This generally is achieved within ten days after therapy is begun. If the sedimentation rate of the blood is elevated, it gradually returns to normal.

In gouty arthritis, patients may experience a substantial improvement within 48 hours with a corresponding drop in blood uric acid. For this reason, the combination of an antihistaminic compound and a diuretic compound employed in my method is also an excellent uricosuric agent.

Thus, by administering standard dosages (e.g. U.S.P. dosages)of the antihistamine and the diuretic at the same time, I have found that both compounds are capable of exerting a unique anti-arthritic effect when used in combination, although the use of either compound by itself has no apparent effect on the course of the disease. When a composition containing both the antihistaminic compound and the diuretic compound is administered to an arthritic patient either by injection (intramuscularly) or orally, the stiffness of the affected joint and its surrounding structures will subside, pain will be reduced, and function of the joint will improve.

The dosage of antihistaminic compound and diuretic compound should be such as to cause a physiological reaction. The composition, comprising an antihistamine and a diuretic, may be prepared in the form of an injectable solution for administration intramuscularly, or it may be compounded into a tablet for oral administration, the dosage in each case depending upon the particular antihistamine and diuretic employed.

The specific antihistamine compounds that I have found to be suitable in the method of my invention are: chlorpheniramine, brompheniramine, diphenhydramine, tripelennamine, and promethazine.

When employed in conjunction with one of the diuretics hereinafter specified, the dosage of these antihistaminic compounds is generally that recommended by the United States Pharmacopoeia as being the average adult dosage. In some instances several times the normal dosage may be employed. The minimum dosage need only be an amount sufficient to cause a physiological reaction. This may vary among different individuals.

The specific diuretic compounds that I have found to be suitable in the method of my invention are:

l. the following Mercurials:

Meralluride, Mercurophylline, Mersalyl, Merithoxylline, Mercumatilin, and Mercaptomerin;

2. the following Benzothiadiazides:

Chlorothiazide, Hydrochlorthiazide, Polythiazide, Flumethazide, Hydroflumethazide, Methylchlorthiazide, Trichlormethiazide, and Benzthiazide;

3. Chlorthalidone;

4. Ethacrynic acid; and

5. Furosemide As in the case of the antihistamines, the minimum dosage of these diuretic compounds is that amount sufficient to cause a physiological reaction, although the normal dosage will be that recommended for the particular diuretic compound in the United States Pharmacopoeia.

Both the antihistamine compound and the diuretic compound may be prepared in the form of an injectable solution using water or any other pharmacologically accepted solvent. They may also be compounded into a tablet for oral ingestion, depending upon the manner chosen by the physician.

I have foundthat any of theforegoing enumerated antihistamine compounds may be combined with any of the foregoing diuretic compounds and the combination administered internally to a person suffering from arthritis, whereupon the remarkable therapeutic effects of my invention are realized.

As previously indicated, the dosage of antihistamine and diuretic is generally a standard dosage as described by the U.S.P., and is such as to cause a physiological reaction. Particularly suitable dosages are set out in Table I hereinafter.

4. Promethazine 12.5 mg. to 200 mg.

Diuretic 1. Mercurials:

Merraluride 0.5 to 2.0 ml. Mercurophylline 0.2 to 2.0 ml.

Mersalyl 0.5 to 2.0 ml. Merithozylline 0.5 to 2.0 ml. Mercumatilin 0.5 to 2.0 ml. Mercaptomerin 0.2 to 2.0 ml. 2. Benzothiadiazide chlorothiazide 500 to 2000 mg. Hydrochlorthiazide 25 to 100 mg. Polythiazide 4 to 8 mg. Flumethazide 500 to 2000 mg. Hydroflumethazide 25 to 50 mg. Methylchlorthiazide 4 to mg. Trichlormethiazide 4 to 8 mg. Benzthiazide 25 to 50 mg. 3. Chlorthalidone 25 to 100 mg. 4. Ethacrynic acid to 200 mg. 5. Furosemide 40 to 80 mg.

Both the antihistaminic compound and the diuretic compound may be prepared in the form of an injectable solution, using water or some other pharmacologically aceptable solvent, or they may be compounded into a tablet for oral ingestion, depending upon the mode of therapy selected by the physician.

In general where my therapeutic composition is to be administered orally, I prefer that standard U.S.P. dosages be given daily. Where the therapeutic composition is injected, however, I prefer that the dosages be given every other day. (Here too, the dosages are preferably standard U.S.P. dosages.)

Table II sets forth the results of a series of clinical tests in which a number of arthritic patients were parenterally treated with anti-arthritic compositions of the present invention. The type of arthritis and its relative severity are indicated in the table. The intramuscular injections were administered every other day, the number of injections being set out in the table. The percentage improvement in each case is also set forth, with complete subsidence of signs and symptoms corresponding to 100 percent.

In each of cases 1,5,9,lO-12, and 32-40 the dosage for each injection consisted of 1 cc of meralluride plus 10 mg chlorpheniramine. In cases l,5,9,l1,12,33-37 .39 and 40 no maintenance therapy was given after the series of injections. In case 10 the maintenance therapy involved an oral dosage of 2 mg polythiazide and 8 mg chlorpheniramine q.i.d. In cases 32 and 38 the maintenance therapy involved a weekly dosage of 1 cc meralluride plus 20 mg chlorpheniramine injected parenterally.

In each of cases 2-4, 7 and 8 the dosage for each injection consisted of 1 cc mersalyl plus 10 mg chlorpheniramine. In cases 3,4, 7 and 8 there was no maintenance therapy. In case 2 the maintenance therapy consisted of one injection weekly for 2 months.

In case 6 the dosage for each injection consisted of 1 cc of mersalyl and mg benadryl. Maintenance therapy involved orally administering 4 mg polythiazide daily and 8 mg chlorpheniramine q.i.d.

In each of cases 13-15, l7,l8,22,23, and 26-31 the dosage for each injection consisted of 1 cc of meralluride plus 20 mg of chlorpheniramine. In cases l3l5, 17,18, and 2630 there was no maintenance therapy. In cases 22 and 31 the maintenance therapy involved 1 dosage weekly of 1 cc of mersalyl plus 20 mg chlorpheneramine, injected parenterally; in case 23, l dosage weekly of 1 cc of mersalyl plus 50 mg tripelennamine, injected parenterally.

In case 16 the dosage for each injection consisted of 1 cc mersalyl plus 50 mg diphenhydramine. Maintenance therapy involved oral administration of a dosage of 50 mg chlorothiazide and 8 mg chlorpheniramine q.i.d.

In each of cases 19,20, 24 and 25 the dosage for each injection was 1 cc mersalyl plus 20 mg chlorpheniramine. No maintenance therapy was given in cases 19,20, and 25. In case 24 therapy was maintained with a weekly parenteral injection of 1 cc mersalyl plus 50 mg diphenhydramine.

In case 21 the dosage for each injection was 1 cc meralluride plus 50 mg diphenhydramine. Therapy was maintained with a weekly parenteral injection of the same dosage.

The data is fully set forth in Table II hereinafter.

TABLE II.[REAT.\IENT OF ARTHRITIS v Duration of Number Percent V I disease prior olinjee improve- Age hex Type of arthritis JOllllS involved to my treatment lions ment til r\l ()steo Left 2--l lingers, both knees 8 months 3 100 35 A1 llands, wrists, knees, ete, -l years 3 100 5 7 1' lo Sinee age 20... ti 100 til M Both knees 1 year (i 00 52 M Cervical to lumbar spine and linger 3 years 3 5: M Both great toes 25 years 6 80 54 F Right wrist, hands and knee 7 years 2 0 60 F Knees, feet, and back 1 year 3 100 l\[ Right knee. 10 years 3 28 M Great toes 14 months G 52 F Ilantls, wrists, knees. 7 years... 6 J0 50 F Ankles and feet 6 months 4 11 F Cervical to lumbar spine. 10 years (i "0 62 M Cervical 12 years 3 10 12 M All lingers, knees l5 yenrs ll. 60 56 F Lumbar, spine, knees" 4 30 00 F llands, lingers, \vri. 3 "U 30 F Right. wrist 3 10!) 56 F \V1isls,l1:m(ls, lmge 10 '0 58 F llotli knees. 3 K1) 83 F lint-k, knees, ankles 11: 0 (it) M Knees (lmspita]i7.etl) 53 liar-k, knees (hospitalized) 5 m 1" ()steo mini klle|'.\ 3 til I Left knet li Hill 70 Al liotll km 1 5 X1! 72 l ln .2 years 3 H0 5! Al tlo 8 months I3 lit; I (ll) 7 rln l year. 13 lit) I Left. knee. int'eetinn, l,el't knee. l innnths Ii Ml I listen... liulh knees it) years I at .\l (lent l'lllmws, wrists, lingers, yrent. Ines tlmspilalizell) do 13 1! M .(l Ines, lltllll knee Hi I M listen. Knees and ankles. 3 Jill M Rheumatoid l'llhnws, wrists, lmlnls 11 I: )hlet) Iiulll lr'llt't'S 3 23 I lsurialie (ervieal Hpine 43 I00 3'. M lll|e|n||ntni l Kneesaml ankles; 5 M ()sten. Right hip ti 100 34 .\l .tl() horse lnm|nn'spine. 7U

It will be understood that while the foregoing clinical tests have demonstrated the results obtained when an arthritic patient undergoes parenteral treatment using my anti-arthritic compositions, comparable results may be obtained by administering such compositions orally.

Variations can, of course, be made without departing from the spirit of my invention.

Having thus described my invention, what I desire to secure and claim by Letters Patent is:

1. A method of alleviating arthritis comprising internally administering to an arthritic person a therapeutic composition comprising an antihistiminic compound selected from the group consisting of chlorpheniramine, brompheniramine, diphenhydramine, tripelennamine, and promethazine and a diruetic compound selected from the group consisting of meralluride, mercurophylline, mersalyl, merithozylline, mercumatilin, mercaptomerin, chlorothiazide, hydrochlorthiazide, polythiazide, flumethazide,

hydroflumethazide, methylchlorthiazide, benzthiazide, chlorthalidone, ethacrynic acid, and furosemide in standard U. S. P. dosages until the arthritic condition diminishes.

2. The method of claim 1 wherein the antihistaminic compound is shlorpheniramine.

3. The method of claim 1 wherein the antihistaminic compound is diphenhydramine.

4. The method of claim 1 wherein the antihistaminic compound is tripelennamine.

5. The method of claim 1 wherein the diuretic compound is meralluride.

6. The method of claim 1 wherein the diuretic compound is mersalyl.

7. The method of claim 1 wherein the diuretic compound is chlorothiazide.

8. The method of claim 1 wherein the diuretic compound is polythiazide.

V UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent NO- 3,726,976 Dated pril 10, 1973 Inventor) JOSEPH GLASSER It. is certified that error appears in the above-identified patent and that said Letters Patent are hereby corrected as shown below:

Column 2, line 47: "theforegoing" should read -the foregoing-- Column 2, Table l: "Merraluride" should read --Meralluride-- Column 3, lines 37-38: "33-37 .39" should read --33-37, 39--. Column 4, line 21: "chlorpheneramine" should read chlorpheniramine'--. Column" 6, line 6:

" shlorpheniramine" should read --chlorpheniramine--.

Signed and sealed this 8th day of January 197M.

(SEAL) Attest:

EDWARD M.ELETCIIEE,JE. RENE D. TEGTMEYER Attesting Officer Acting Commissioner of Patents 

2. The method of claim 1 wherein the antihistaminic compound is shlorpheniramine.
 3. The method of claim 1 wherein the antihistaminic compound is diphenhydramine.
 4. The method of claim 1 wherein the antihistaminic compound is tripelennamine.
 5. The method of claim 1 wherein the diuretic compound is meralluride.
 6. The method of claim 1 wherein the diuretic compound is mersalyl.
 7. The method of claim 1 wherein the diuretic compound is chlorothiazide.
 8. The method of claim 1 wherein the diuretic compound is polythiazide. 